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A recent randomized controlled study showed that 66.7% (66/99) and 37.4% (37/99) of people undergoing remote electrical neuromodulation (REN), a novel non-pharmacological migraine treatment, achieve pain relief and pain freedom, respectively, at 2 h post-treatment. The participants who completed the 6-weeks double-blind phase of this study were offered to participate in an open-label extension (OLE) with an active REN device. This study investigated the clinical use of REN, focusing on its potential in reducing the use of acute migraine medications. The parent study for this open-label extension (OLE) was a randomized, double-blind, sham-controlled study of acute treatment conducted on 296 participants enrolled at 12 sites in the USA and Israel. This study included a run-in phase, in which migraine attacks were treated with usual care, and an 8-weeks double-blind treatment phase. One hundred sixty participants continued in an 8-weeks OLE phase in which they could incorporate a REN device into their usual care. Medication use rate (percentage of participants who treated their attacks only with REN and avoided medications in all their attacks) and pain outcomes at 2 h post-treatment were compared between the OLE and the run-in phase in a within-subject design. The analyses were performed on 117 participants with episodic migraine. During the OLE, 89.7% of the participants treated their attacks only with REN and avoided medications in all their attacks compared with 15.4% in the run-in phase ( < 0.0001). The rates of pain relief and pain-free in at least 50% of the treatments at 2 h post-treatment were comparable (pain relief: 58.1% in the run-in phase and 57.3% in the OLE, = 0.999; pain-free: 23.1% in the run-in vs. 30.8% in the OLE, = 0.175). REN may reduce the use of acute migraine medications. Thus, incorporating REN into usual care may reduce the risk for medication overuse headache (MOH). Future studies should evaluate whether REN reduces the use of acute migraine medications in a population at risk for MOH.
Cost utility analysis is important for measuring the impact of chronic disease and helps clinicians and policymakers in patient management and policy decisions, but generic preference-based measures are not always considered in clinical studies.
Neuroimaging studies have demonstrated that altered activity in somatosensory and motor cortices play a key role in pain chronification. Neurofeedback training of sensorimotor rhythm (SMR) is a tool which allow individuals to self-modulate their brain activity and to produce significant changes over somatomotor brain areas. Several studies have further shown that neurofeedback training may reduce pain and other pain-related symptoms in chronic pain patients. The goal of the present study was to analyze changes in SMR power and brain functional connectivity of the somatosensory and motor cortices elicited by neurofeedback task designed to both synchronize and desynchronize the SMR power over motor and somatosensory areas in fibromyalgia patients. Seventeen patients were randomly assigned to the SMR training ( = 9) or to a sham protocol ( = 8). All participants were trained during 6 sessions, and fMRI and EEG power elicited by synchronization and desynchronization trials were analyzed. In the SMR training group, four patients achieved the objective of SMR modulation in more than 70% of the trials from the second training session (good responders), while five patients performed the task at the chance level (bad responders). Good responders to the neurofeedback training significantly reduced pain and increased both SMR power modulation and functional connectivity of motor and somatosensory related areas during the last neurofeedback training session, whereas no changes in brain activity or pain were observed in bad responders or participants in the sham group. In addition, we observed that good responders were characterized by reduced impact of fibromyalgia and pain symptoms, as well as by increased levels of health-related quality of life during the pre-training sessions. In summary, the present study revealed that neurofeedback training of SMR elicited significant brain changes in somatomotor areas leading to a significant reduction of pain in fibromyalgia patients. In this sense, our research provide evidence that neurofeedback training is a promising tool for a better understanding of brain mechanisms involved in pain chronification.
Acute pain trajectories are associated with long-term outcomes such as persistent pain and functional disability in adults. However, there are limited data on acute postoperative pain trajectories in the pediatric population. The aims of this study were to investigate acute postoperative pain trajectories, their predictors, and their impact on long- term outcomes in adolescents with idiopathic scoliosis.
Transcranial direct current stimulation (tDCS) is used for various chronic pain conditions, but experience with tDCS for acute postoperative pain is limited. This study investigated the effect of tDCS vs. sham stimulation on postoperative morphine consumption and pain intensity after thoracotomy.
We conducted a feasibility 2×2 factorial trial comparing N-methyl-D-aspartate (NMDA) antagonists (intravenous ketamine and oral memantine) versus placebo and intravenous steroids versus placebo, in patients having elective video-assisted thoracic surgery lobectomies, at St. Joseph's Hamilton, Canada, and Cleveland Clinic, Cleveland, USA. Our feasibility objectives were: 1) recruitment rate/week; 2) recruitment of ≥90% of eligible patients; and 3) >90% follow-up. Secondary objectives were incidence and intensity of persistent post-surgical pain (PPSP) and other clinical and safety outcomes.
Osteoarthritis is the most prominent form of arthritis, affecting approximately 15% of the population in the United States. Knee osteoarthritis (KOA) has become one of the leading causes of disability in older adults. Besides knee replacement, there are no curative treatments for KOA, so persistent pain is commonly treated with opioids, acetaminophen, and nonsteroidal anti-inflammatory drugs. However, these drugs have many unpleasant side effects, so there is a need for alternative forms of pain management. We sought to test the efficacy of a dietary intervention to reduce KOA.
Tumor-related cancer pain often comprises mixed pain with both nociceptive and neuropathic components. Whether tumor-related cancer pain includes a neuropathic component impacts the therapeutic strategy. The aim of this cross-sectional study was to investigate the usefulness of two screening tools for neuropathic pain, painDETECT and Self-Report Leeds Assessment of Neuropathic Symptoms and Signs (S-LANSS), in identifying the neuropathic component of mixed pain among patients with tumor-related cancer pain.
Relief of cancer-related pain remains challenging despite the availability of a range of opioid and non-opioid medications. Animal models demonstrate that T lymphocytes may mediate analgesia by producing endogenous opioids, but definitive clinical data are limited. Adoptive transfer of ex vivo activated T cell products (ACT) is being tested as an anti-cancer therapy. We retrospectively reviewed the medical charts of 357 patients with various malignancies who received three intravenous infusions of autologous cytokine-activated T cell-enriched products. Among these were fifty-five (55) patients who required opioids for moderate or severe cancer-related pain. Opioid dosage and cancer pain score were recorded daily for 2 consecutive weeks prior to and 2 weeks after the ACT infusions. The average oral morphine equivalent doses (OMED) and cancer pain scores were significantly decreased following the ACT infusions. The proportion of patients with breakthrough pain also declined. Moreover, higher frequencies of expanded CD3+, CD3+/CD4+, and CD3+/CD8+ T cells within the ACT product were associated with favorable analgesic effects. Transient elevations in CD3+ and CD3+/CD8+ T cell subpopulations and decreases in CD4CD25 Treg were observed in patients' blood after the ACT. In conclusion, ACT was capable of reducing cancer pain severity and opioid consumption and favorably modulating peripheral blood T cell populations.
Brain derived neurotrophic factor (BDNF) and the high affinity receptor tropomyosin receptor kinase B (TrkB) have important roles in neuronal survival and in spinal sensitization mechanisms associated with chronic pain. Recent clinical evidence also supports a peripheral role of BDNF in osteoarthritis (OA), with synovial expression of TrkB associated with higher OA pain. The aim of this study was to use clinical samples and animal models to explore the potential contribution of knee joint BDNF / TrkB signalling to chronic OA pain.BDNF and TrkB mRNA and protein were present in knee synovia from OA patients (16 women, 14 men, median age 67 [IQR: 61 – 73]). There was a significant positive correlation between mRNA expression of NTRK2 (TrkB) and the pro-inflammatory chemokine fractalkine in the OA synovia.Using the surgical medial meniscal transection (MNX) model and the chemical monosodium iodoacetate (MIA) model of OA pain in male rats, the effects of peripheral BDNF injection, versus sequestering endogenous BDNF with TrkB-Fc chimera, on established pain behaviour were determined. Intra-articular injection of BDNF augmented established OA pain behaviour in MIA rats, but had no effect in controls. Intra-articular injection of the TrkB-Fc chimera acutely reversed pain behaviour to a similar extent in both models of OA pain (weight-bearing asymmetry MIA: -11±4%, MNX: -12±4%), compared to vehicle treatment. Our data suggesting a contribution of peripheral knee joint BDNF / TrkB signalling in the maintenance of chronic OA joint pain support further investigation of the therapeutic potential of this target.